IP Library Granted Patent US 12,365,929
Granted Patent B2
US 12,365,929 · App. 18/327,434 · Granted Jul 22, 2025

Reconfigurable DNA nano-tweezer

Inventors: Nicholas Stephanopoulos (Scottsdale, AZ); Minghui Liu (Chandler, AZ)
Assignee: ARIZONA BOARD OF REGENTS ON BEHALF OF ARIZONA STATE UNIVERSITY
C12P19/34C12N15/111B82Y5/00B82Y40/00C12N2310/122C12N2310/3181C12N2310/531
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,365,929
App. No.
18/327,434
Granted
Jul 22, 2025
Kind
B2
Abstract

A photocaged DNA nano-tweezer and methods of using said photocaged DNA nano-tweezer are described. In particular, provided herein is a DNA nano-tweezer comprising a hairpin with a single-stranded loop that comprises a first arm and a second arm; and a trigger strand complementary to the single-stranded loop and comprising at least one photocaged residue with a protecting group.

Claims (14)

1. A DNA nano-tweezer comprising:

a DNA hairpin with a single-stranded loop, wherein the loop has at least two arms with a distance of between about 4 nm to about 18 nm between the distal tip of the at least two arms; and

a DNA trigger strand complementary to the single-stranded loop and comprising at least one photocaged residue,

wherein the DNA nano-tweezer is in a closed conformation until exposed to a pulse of light whereby the photocaged residue is released and the trigger strand is hybridized to the single-stranded loop forming an open conformation wherein the distance between the at least two arms is at least 18 nm.

2. The DNA nano-tweezer of claim 1 , wherein the single-stranded loop and the trigger strand are selected from the group consisting of a poly-A loop, a poly-T loop, a poly-G loop, and a poly-C loop.

3. The DNA nano-tweezer of claim 1 , wherein the photocaged residue comprises a 6-nitropiperonyloxymethyl protecting group.

4. The DNA nano-tweezer of claim 1 additionally comprising a ligand.

5. The DNA nano-tweezer of claim 1 additionally comprising a fluorescent label.

6. The DNA nano-tweezer of claim 1 , wherein the DNA nanotweezer additionally comprises a locking strand.

7. The DNA nano-tweezer of claim 6 , wherein the locking strand comprises an o-nitrobenzyl ester photocleavable backbone.

8. The DNA nano-tweezer of claim 1 , wherein the light is UV light.

9. The DNA nano-tweezer of claim 1 . wherein the light is between about 300 nm and about 400 nm.

10. The DNA nano-tweezer of claim 1 , wherein the pulse of light is between about 1 second and about 10 seconds.

11. The DNA nano-tweezer of claim 1 , wherein the distance between the distal tip of the at least two arms is between about 4 nm and about 16 nm.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 9, 2023
From: STEPHANOPOULOS, NICHOLAS; LIU, MINGHUI
To: ARIZONA BOARD OF REGENTS ON BEHALF OF ARIZONA STATE UNIVERSITY
Reel/Frame 065507/0667 →
Continuity (3)
Division 16653235 · Oct 15, 2019
Provisional Application 62746139 · Oct 16, 2018
Related Publication 20240011065A1 · Jan 11, 2024
References Cited (48)
US 11547997B2 · Green et al. · 2023 [cited by applicant]
US 11708594B2 · Stephanopoulos · 2023 [cited by examiner]
US 20180016569A1 · Fu · 2018 [cited by applicant]
US 20200289658A1 · Stephanopoulos et al. · 2020 [cited by applicant]
WO 2018187687 · 2018 [cited by applicant]
Asanuma, H., et al. “Photoregulation of the formation and dissociation of a DNA duplex by using the cis-trans somerization of azobenzene.” Angewandte Chemie International Edition 38.16 (1999): 2393-2395. [cited by applicant]
Bruns, C. J., et al. “Rotaxane-based molecular muscles.” Accounts of chemical research 47.7 (2014): 2186-2199. [cited by applicant]
Buff, M. et al. “Light-Activatable Nucleic Acids ‘Caged’at the Nucleobases.” Chimia International Journal for Chemistry 63.5 (2009): 261-264. [cited by applicant]
Deiters, A. “Light activation as a method of regulating and studying gene expression.” Current opinion in chemical biology 13.5-6 (2009): 678-686. [cited by applicant]
Douglas, S., et al. Erratum: Self-assembly of DNA into nanoscale three-dimensional shapes. Nature 459, 1154 (2009). [cited by applicant]
Douglas, S. M., et al. “A logic-gated nanorobot for targeted transport of molecular payloads.” Science 335.6070 (2012): 831-834. [cited by applicant]
Doye, JPK, et al. “Coarse-graining DNA for simulations of DNA nanotechnology.” Physical Chemistry Chemical Physics 15.47 (2013): 20395-20414. [cited by applicant]
Fields, A.P. et al. Euler buckling and nonlinear kinking of doublestranded DNA, 2013, Nucleic acids research, 41 (21): 9881-9890. [cited by applicant]
Fu, J., et al. “Multi-enzyme complexes on DNA scaffolds capable of substrate channelling with an artificial swinging arm.” Nature nanotechnology 9.7 (2014): 531. [cited by applicant]
Funke, J. J., et al. “Placing molecules with Bohr radius resolution using DNA origami.” Nature nanotechnology 11.1 (2016): 47-52. [cited by applicant]
Funke, J. J., et al. “Uncovering the forces between nucleosomes using DNA origami.” Science advances 2.11 (2016): e1600974. [cited by applicant]
Goddard, N. L., et al. “Sequence dependent rigidity of single stranded DNA.” Physical review letters 85.11 (2000): 2400. [cited by applicant]
Harrison, RM et al. Coarse-grained modelling of strong DNA bending i: Thermodynamics and comparison to an experimental “molecular vice”, 2015 arXiv preprint arXiv:1506.09005. [cited by applicant]
Hong, F, et al. “DNA origami: scaffolds for creating higher order structures.” Chemical reviews 117.20 (2017): 12584-12640. [cited by applicant]
Huang, F, et al. “DNA branch migration reactions through photocontrollable toehold formation.” Journal of the American Chemical Society 135.21 (2013): 7967-7973. [cited by applicant]
Kamiya, Y. et al. “Light-driven DNA nanomachine with a photoresponsive molecular engine.” Accounts of chemical research 47.6 (2014): 1663-1672. [cited by applicant]
Ke, Y., et al. “Three-dimensional structures self-assembled from DNA bricks.” science 338.6111 (2012): 1177-1183. [cited by applicant]
Le, J. V., et al. “Probing nucleosome stability with a DNA origami nanocaliper.” ACS nano 10.7 (2016): 7073-7084. [cited by applicant]
Li, S., et al. “A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo.” Nature biotechnology 36.3 (2018): 258. [cited by applicant]
List, J., et al. “Long-range movement of large mechanically interlocked DNA nanostructures.” Nature communications 7.1 (2016): 1-7. [cited by applicant]
Liu, M., et al. “A DNA tweezer-actuated enzyme nanoreactor.” Nature communications 4.1 (2013): 1-5. [cited by applicant]
Lo, P K, et al. “Loading and selective release of cargo in DNA nanotubes with longitudinal variation.” Nature chemistry 2.4 (2010): 319. [cited by applicant]
Lusic, H., et al. “A new photocaging group for aromatic N-heterocycles.” Synthesis 2006.13 (2006): 2147-2150. [cited by applicant]
Lusic, H., et al. “Photochemical DNA activation.” Organic letters 9.10 (2007): 1903-1906. [cited by applicant]
Marras, A. E., et al. “Programmable motion of DNA origami mechanisms.” Proceedings of the National Academy of Sciences 112.3 (2015): 713-718. [cited by applicant]
Pirrung, MC et al. “Photoremoveable protecting groups in DNA synthesis and microarray fabrication,” Chapter 6 of Dynamic Studies in Biology: Phototriggers, Photoswitches and Caged Biomolecules, 2005. [cited by applicant]
Powell, J. T., et al. “DNA origami rotaxanes: tailored synthesis and controlled structure switching.” Angewandte Chemie 128.38 (2016): 11584-11588. [cited by applicant]
Rothemund, PWK, et al. “Design and characterization of programmable DNA nanotubes.” Journal of the American Chemical Society 126.50 (2004): 16344-16352. [cited by applicant]
Rothemund, PWK. “Folding DNA to create nanoscale shapes and patterns.” Nature 440.7082 (2006): 297-302. [cited by applicant]
Samanta, S, et al. “Photoswitching azo compounds in vivo with red light.” Journal of the American Chemical Society 135.26 (2013): 9777-9784. [cited by applicant]
Sulc, P, et al. “Sequence-dependent thermodynamics of a coarse-grained DNA model.” The Journal of chemical physics 137.13 (2012): 135101. [cited by applicant]
Vologodskii, A. et al. “Strong bending of the DNA double helix.” Nucleic acids research 41.14 (2013): 6785-6792. [cited by applicant]
Walbert, S., et al. “Photolabile protecting groups for nucleosides: Mechanistic studies of the 2-(2-nitrophenyl) ethyl group.” Helvetica Chimica Acta 84.6 (2001): 1601-1611. [cited by applicant]
Wang, X. et al. “Defining single molecular forces required to activate integrin and notch signaling.” Science 340.6135 (2013): 991-994. [cited by applicant]
Wei, B. et al. “Complex shapes self-assembled from single-stranded DNA tiles.” Nature 485.7400 (2012): 623-626. [cited by applicant]
Winfree, E., et al. “Design and self-assembly of two-dimensional DNA crystals.” Nature 394.6693 (1998): 539-544. [cited by applicant]
Yan, H., et al. “DNA-templated self-assembly of protein arrays and highly conductive nanowires.” science 301.5641 (2003): 1882-1884. [cited by applicant]
Zhang, DY, et al. “Dynamic DNA nanotechnology using strand-displacement reactions.” Nature chemistry 3.2 (2011): 103. [cited by applicant]
Zheng, J, et al. “From molecular to macroscopic via the rational design of a self-assembled 3D DNA crystal.” Nature 161.7260 (2009): 74-77. [cited by applicant]
Zhou, C., et al. “Reversible regulation of protein binding affinity by a DNA machine.” Journal of the American Chemical Society 134.3 (2012): 1416-1418. [cited by applicant]
Liu et al (Nat. Commun., vol. 4, 2127 (2013)) (Year: 2013). [cited by applicant]
Zhang et al (Nature Chemistry, vol. 3, pp. 103-113 (2011)) (Year: 2011). [cited by applicant]
Kamiya et al (Accounts of Chemical Research, vol. 47, No. 6, pp. 1663-1672 (2014)) (Year: 2014). [cited by applicant]